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OBJECTIVE: To develop an objective method for quantifying venous vasculature in brain parenchyma on susceptibility-weighted imaging (SWI). To apply this technique in multiple sclerosis (MS) patients and in healthy controls (HC). BACKGROUND: SWI is a MRI application that can directly image cerebral veins by exploiting venous blood oxygenation. DESIGN/METHODS: Sixty-two (62) MS patients (44 relapsing-remitting and 18 secondary-progressive) and 33 age- and sex-matched HC were imaged on a 3T GE scanner using pre-contrast SWI. A subset of MS patients (50) and HC (7) obtained SWI-post gadolinium contrast sequence (0.1 mMol/Kg Gd-DTPA with 10 min delay). In-house developed segmentation algorithm, based on a 3D multi-scale line filter, was applied for vein segmentation. Absolute volumetric measurement for total vein vasculature was performed in milliliters (ml) and the relative venous intracranial fraction (VIF) was obtained to correct for head size and amount of brain atrophy. The size of individual veins was measured in mm and 4 groups were created according to their mean diameter: <0.3mm, 0.3-0.6mm, 0.6-0.9mm and >0.9 mm. Voxel brain average distance-from-vein maps was also calculated with higher distance indicating fewer veins. RESULTS: A significantly lower absolute venous volume was detected in MS patients compared to HC, both in pre-contrast (67.5 vs. 82.7ml, -18.3%, p<0.001) and post-contrast (70.4 vs. 87.1ml, -19.1%, p<0.011) images. The VIF was significantly lower in MS patients (p<0.001). The highest mean diameter difference was found for the smallest veins (<0.3 mm), both on pre- (p<0.001) and post-contrast (p<0.018) images. The distance-from-veins was also significantly higher in MS patients (p<0.001). CONCLUSIONS/RELEVANCE: We developed and validated a quantitative vein segmentation method that showed altered visibility of venous vasculature on SWI pre- and post-contrast images in MS patients. These findings suggest severely compromised brain venous system in MS patients.

OBJECTIVE: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral perfusion in patients with multiple sclerosis (MS). BACKGROUND: CCSVI is a vascular condition described in MS patients, characterized by stenoses of the main extracranial veins with hampered cerebral venous outflow. We hypothesized that the impaired venous outflow contributes to hypoperfusion of brain parenchyma. DESIGN/METHODS: Sixteen consecutive relapsing-remitting MS patients (mean age 36.1yrs, mean disease duration 7.5yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC), were scanned on a GE 3T scanner using dynamic susceptibility contrast enhanced perfusion-weighted imaging (PWI). Cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM), normal appearing (NA) GM, NAWM, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Diagnosis of CCSVI was established based on the venous hemodynamic (VH) Doppler criteria (Zamboni, JNNP, 2009) and the severity was based on fulfilled VH criteria (score 0-5) and VH insufficiency severity score (VHISS) (score 0-16). RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between VH criteria and VHISS, and CBF, CBV and MTT in all examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for lower CBF and higher VHISS in the GM, WM, NAGM and NAWM (r= -0.70 to -0.72, p<0.002), and in the thalamus, caudate, putamen, hippocampus, nucleus accumbens (r= -0.6 to -0.72, p<0.008). The correlation coefficients for CBV and MTT were in a range between r= -0.5 to -0.65. No relationship was observed for NC. CONCLUSIONS/RELEVANCE: This study demonstrates that severity of CCSVI is directly associated with hypoperfusion of the brain parenchyma in MS. Supported by: Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.

OBJECTIVE: To investigate the cerebrospinal fluid (CSF) dynamics in Sylvius aqueduct in multiple sclerosis (MS) patients versus healthy controls (HC) and to define correlates with other specific disease metrics. BACKGROUND: CSF velocity and flow dynamics, as measured by MRI in MS patients, may be impaired and associated with higher disease activity. DESIGN/METHODS: Fifty eight (5 consecutive MS patients (41 RR and 17 SP) with mean age 45.3 yrs, mean disease duration 13 yrs and median EDSS 4.0 and 22 age- and sex-matched HC were scanned on a GE 3T scanner. A two-dimensional, phase-contrast gradient-echo MR acquisition using peripheral cardiac gating, with in-plane resolution 0.39x.039mm2 and 32 phases, corresponding to a full cardiac cycle, was collected on one 4mm thick slice positioned perpendicular to the Sylvius aqueduct. In addition to CSF measures, we calculated T2, T1- and contrast enhancing (CE) lesion volume (LV), global, tissue-specific and central brain atrophy measures. RESULTS: All CSF flow and velocity measures were significantly altered in the patients with MS, compared to HC. Net CSF flow in the aqueduct, which physiologically is towards 4th ventricle, was significantly lower in MS patients than in HC (3.8 vs. 8.4, p=0.011). There were no CSF dynamics differences between RR and SP MS patients. In MS patients, lower net CSF flow was significantly related to a higher number of relapses in the previous year (r=-0.28, p=0.029) and longer disease duration (r=-0.25, p=0.048). The lower CSF flow was related to central atrophy, as measured by the enlargement of the lateral ventricle volume and third ventricle width (r=0.3, p<0.02). CONCLUSIONS/RELEVANCE: This study shows that CSF flow is significantly altered in MS patients, compared to HC. Altered CSF dynamics may play an important role in the pathophysiology of MS disease process and warrants further investigation.

OBJECTIVE: To ascertain the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in a large cohort of patients with multiple sclerosis (MS), patients with other neurological diseases (OND) and in normal controls (NC), by using specific proposed Doppler criteria (Zamboni et al, JNNP, 2009). BACKGROUND: CCSVI is a complex vascular condition characterized by anomalies of the main extracranial cerebrospinal (CS) venous routes that interfere with the normal CS venous outflow. This condition was previously associated with clinically definite MS. DESIGN/METHODS: Cross-sectional study that will enroll consecutive 1700 subjects at one MS center including: 1000 adult patients with possible and definite MS (50 clinically isolated syndrome, 50 radiologically isolated syndrome, 500 relapsing-remitting, 300 secondary-progressive, 50 primary-progressive MS and 50 neuromyelitis optica). A comparative group will include 300 OND patients and 300 adult age- and sex-matched NC. Fifty pediatric patients (<18 yrs) with acquired demyelinating diseases (MS and acute disseminated encephalomyelitis) and 50 pediatric NC will be assessed. All participants will undergo clinical examination and a Doppler scan of the head and neck. All MS patients and a subcohort of NC and OND will undergo an MRI of the brain. A consecutive subgroup (MS, NC and OND) will have also an MRI of the veins of the neck to corroborate the Doppler diagnosis of CCSVI. The Doppler, and MRI evaluators are blinded to the subject status. The prevalence and severity of venous hemodynamic abnormalities identified in the different groups will be analyzed. Data will be unblinded at three predetermined time-points based on the number of subjects enrolled: at 500, 1000 and 1700 subjects respectively. RESULTS: As of 1 Nov 2009, 473 subjects signed informed consent. The initial interim analysis following the first 500 subjects is scheduled for December 2009. CONCLUSIONS/RELEVANCE: The interim results of the first 500 enrolled subjects will be presented.
(to be presented at the American Annual Neurology Conference in Toronto April 10 - 17, 2010)

OBJECTIVE: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and iron deposition in the brain of multiple sclerosis (MS) patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter (DGM) structures and lesions, as measured by susceptibility-weighted imaging (SWI). To preliminarily define the relationship between iron measures and disability outcomes. BACKGROUND: CCSVI is a vascular picture recently described in MS patients that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. DESIGN/METHODS: Sixteen (16) consecutive relapsing-remitting MS patients (mean age 36.17.3 yrs, mean disease duration 7.5 1.9 yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC) were scanned on a GE 3T scanner, by using SWI. Iron concentration was measured in the following DGM structures: thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Iron concentration was also measured in T2, T1, SWI phase and SWI magnitude lesions. Diagnosis of the CCSVI was established based on the previously published VH Doppler criteria (Zamboni, JNNP, 2009). RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between higher number of VH criteria and higher iron concentration in T2 (r=0.64, p=0.007) and T1 (r=0.56, p=0.023) lesion volumes. The only DGM structure that correlated significantly with VH criteria was globus pallidus (r=0.58, p=0.019). No relationship was observed for NC. Higher iron concentration in DGM structures was predictive of higher disability status (EDSS) in almost all examined regions. The highest correlations were detected for thalamus (r=0.79, p<0.0001) and red nucleus (r=0.7, p=0.005). CONCLUSIONS/RELEVANCE: The findings from this pilot study suggest that CCSVI may be an important mechanism leading to iron deposition in brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a strong predictor of disability progression in patients with MS. Supported by: Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.

OBJECTIVE: To develop an objective MRI technique for quantifying the cerebrospinal fluid (CSF) flow in Sylvius aqueduct. To apply this technique in a pilot study in multiple sclerosis (MS) patients versus normal controls (NC) and provide further correlates with other MRI specific disease metrics. BACKGROUND: Non-invasive MRI investigation of the CSF dynamics in MS has not been previously reported. DESIGN/METHODS: For consistency and objective quantification of the antegrade (towards 4th ventricle), retrograde (towards 3rd ventricle) and net CSF flow rates, a semi-automated program was developed. The CSF flow quantification technique was validated on a tube phantom, using a power injector which provided a controlled flow rate. 2 NC and 2 MS patients were scanned and rescanned within a week, to test reproducibility. Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched NC were scanned on a GE 3T scanner using a two-dimensional phase-contrast gradient-echo MR technique with high spatial-temporal resolution (in-plane resolution 0.39x.039mm2 and 32 phases, corresponding to a full cardiac cycle) on one 4mm thick slice positioned perpendicular to the Sylvius aqueduct. In addition to CSF flow measures, lesion volume (LV) and atrophy MRI outcomes were calculated. RESULTS: Net CSF flow scan-rescan reproducibility was 10.9%. Net CSF flow rate (stroke volume) was significantly lower in MS patients than in NC (p=0.038). In MS patients, T1-LV was strongly correlated with CSF retrograde (r=0.71, p=0.002) and antegrade flow rates (r=-0.64, p=0.008). T2-LV was also related to CSF flow rate (0.58, p=0.019). Lower net CSF flow rate was related to gray matter (r=-0.63, p=0.009), whole brain and cortical atrophy (p<0.037). CONCLUSIONS/RELEVANCE: CSF flow rate in the Sylvius aqueduct is significantly lower in MS patients than in NC. In MS patients, robust correlations between higher LVs, and advanced atrophy, and altered flow rate measures were found.

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I would like to know if anyone has seen this study and is it not significant?
In the conclusion: "the impact of treating vascular comorbidities on disease progression deserves investigation."
Note study funding...... 8,983 patients.
Any comments appreciated. If it is already posted , I apologize , can't find it. Have not read full article.

Background: Vascular comorbidity adversely influences health outcomes in several chronic conditions. Vascular comorbidities are common in multiple sclerosis (MS), but their impact on disease severity is unknown. Vascular comorbidities may contribute to the poorly understood heterogeneity in MS disease severity. Treatment of vascular comorbidities may represent an avenue for treating MS.

Methods: A total of 8,983 patients with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry participated in this cohort study. Time from symptom onset or diagnosis until ambulatory disability was compared for patients with or without vascular comorbidities to determine their impact on MS severity. Multivariable proportional hazards models were adjusted for sex, race, age at symptom onset, year of symptom onset, socioeconomic status, and region of residence.

Results: Participants reporting one or more vascular comorbidities at diagnosis had an increased risk of ambulatory disability, and risk increased with the number of vascular conditions reported (hazard ratio [HR]/condition for early gait disability 1.51; 95% confidence interval [CI] 1.41–1.61). Vascular comorbidity at any time during the disease course also increased the risk of ambulatory disability (adjusted HR for unilateral walking assistance 1.54; 95% CI 1.44–1.65). The median time between diagnosis and need for ambulatory assistance was 18.8 years in patients without and 12.8 years in patients with vascular comorbidities.

Conclusions: Vascular comorbidity, whether present at symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in multiple sclerosis. The impact of treating vascular comorbidities on disease progression deserves investigation.

Study funding: Supported in part by the NIH, National Institute of Child Health and Human Development, and Multidisciplinary Clinical Research Career Development Program Grant K12 HD04909. The NARCOMS Registry is supported by the Consortium of Multiple Sclerosis Centers.

Disclosure: Author disclosures are provided at the end of the article.

An interview about the above mentioned study
http://www.aan.com/news/?event=read&article_id=8754and an exerpt thereof
«AAN.com: Do vascular comorbidities affect disease progression among patients with MS by promoting and potentiating cerebrovascular disease?
Marrie: We did not examine cerebrovascular disease in this study, though this is an important issue—and a potential explanation for our findings. The question requires further study.»

I found the above very interesting. Especially since I just read the Rocky Mtn MS Center publication InforMS. There's an article in it "RMMSC Weighs In on CCSVI" written by Drs. J Corboy, T VOLLMER(!) and P Daily. Basically, the article is warning us to wait until more studies are done. Not a completely accurate article, i.e. referring to vascular surgery being risky with "several instances" of serious complication and/or patient death...risk of procedure greater than any potential (unproven) venefit."

What the heck, Dr Vollmer? and he was involved in the above cited study?

More than 600 multiple sclerosis patients came to Hamilton hoping to hear about a possible cure to what until now has been a mystery disease with few treatment options.

Many left Michelangelo's Event and Conference Centre Saturday frustrated that it will be years before they can "be liberated" as the treatment has been called by Dr. Paolo Zamboni, the Italian surgeon who has pioneered it.

"I'm 70 years old, where do I fit in?" said Barbara Farraway, of Hamilton, who was diagnosed with MS 20 years ago. "It's hard to wait when it's progressing."

Farraway and her husband took little comfort in reassurances that research is being fast-tracked to test Zamboni's theory MS is a vascular disease involving blocked veins improperly draining blood from the brain and spinal cord.

While the information session was put on by the MS Society of Canada, there was a lot of anger at the organization and its American counterpart over the decision to give no money to high-profile studies in Hamilton and Buffalo when they handed out $2.4 million in funding Friday to test the theory called chronic cerebrospinal venous insufficiency (CCSVI).

"One of my questions is why the MS Society didn't back the Hamilton project because it's going to slow the process down," said Jim Palango, of Brantford, about the society's refusal to provide any information about why certain studies weren't recommended for funding by its international review panel. "Will more donations speed up the process and if so, let's get on the bandwagon to help St. Joseph's since the MS Society of Canada is not supporting them."
The lead researcher in Buffalo says he suspects his study and the one in Hamilton, being done by St. Joseph's, McMaster University and Hamilton Health Sciences, weren't funded because of their ties to Zamboni. Both consulted Zamboni about their studies.

"I think probably it has to do with it," said Dr. Robert Zivadinov, director of the Buffalo Neuroimaging Analysis Center, and one of the presenters at the information session. "They wanted the people who are not connected with the way Zamboni is doing this."Researchers in Buffalo and Hamilton say they will continue with their studies despite being shut out of funding.

Hamilton's study has about $350,000 to get started, mostly donated from MS patients.

this does not come as a big shock. but, hopefully this will get more individuals and groups raising money for ms to make sure the money gets to researchers and doctors that are testing and treating ccsvi and hopefully ctos soon. kinda reminds me of govt. it's our tax dollars but seems like they aren't listenig much. the money the ms society has was collected to help us but seems like they aren't listening. well, it is harder to get out of paying taxes but very easy to give what we donate to the groups like buffalo, haacke, zambonni etc. there is ccsvi alliance coming soon. i feel these groups will represent us not a bunch of over paid CEO'S!!

Not able to see full article but this seems to suggest autoimmune activity is not the culprit: <shortened url>

A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it
- Max Planck

A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it
- Max Planck

Using Doppler ultrasound and venograms, they found severe extracranial venous stenosis in MS patients. They suggested that a venous obstruction in the neck caused a reflux back into the brain, which led to edema and demyelination.

We examined the blood flow and the cross-sectional area of the internal jugular veins using Doppler ultrasound (Vivid 7 PRO, GE Health Japan, Tokyo) in 17 MS (8 males and 9 females; 20-58 years of age, median 38 years) and 11 neuromyelitis optica (NMO) Japanese patients (1 male and 10 females; 23-60 years of age, median 44 years). Nine of the 11 NMO patients were seropositive for anti-aquaporin4 antibodies.

We did not find any obstruction or stenosis of the internal jugular veins in any patient. Other disorders such as bilateral internal and external jugular venous ligation or radical neck dissection, which result in venous stasis, are not known causes of demyelination in the central nervous system.

Our data also does not support the hypothesis of CCSVI theory, despite the fact that our study was limited to a small group of patients and the examination was performed only using Doppler ultrasound.PMID: 21735737 [PubMed - in process]

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